Investigations of inherited retinal degeneration of c3H mice and RCS rats are continuing. We are currently interested in the study of cyclic nucleotide metabolism in these retinas. Our observations indicate that cyclic GMP is the predominant cyclic nucleotide of the photoreceptor cells and that cyclic AMP is concentrated in the inner layers of the rodent retina. In the inherited retinal degeneration both of C3H mice and RCS rats, an abnormality in cyclic GMP metabolism of the photoreceptor cells is detectable a few days before the photoreceptor cells degenerate. In the C3H retina, an abnormality in cyclic GMP metabolism results from a deficiency in cyclic GMP phosphodiesterase activity of the photoreceptor cells. In the RCS retina, an abnormality in cyclic GMP metabolism of the photoreceptor cells is induced by the debris which accumulates in this disorder. The mouse disease has now been simulated in normal eye rudiments of Xenopus laevis (clawed toad) embryos in culture, using selective inhibitors of cyclic nucleotide phosphodiesterase which cause elevated level of cyclic GMP. The biochemical action of cyclic GMP in normal photoreceptor cells and its possible role in visual cell degeneration in the mouse, rat and toad disorders is the focus of our ongoing studies. BIBLIOGRAPHIC REFERENCES: Farber, D.B. and Lolley, R.N. Calcium and magnesium content of rodent photoreceptor cells as inferred from studies of retinal degeneration. Exp. Eye Res. 22: 219, 1976. Lolley, R.N. and Farber, D.B. Abnormal guanosine 3', 5'-monophosphate during photoreceptor degeneration in the inherited retinal disorder of C3H/HeJ mice. Ann. Ophthalmol. 8: 469, 1976.